Human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2) are retroviruses that cause acquired immunodeficiency syndrome (AIDS) in humans. AIDS results from low levels of CD4-positive T-lymphocytes in HIV-infected individuals.
HIV-1 infects T-lymphocytes, monocytes/macrophages, dendritic cells and microglia. All of these cells express the surface glycoprotein CD4 which serves as a receptor for HIV-1 and HIV-2. Efficient entry of HIV-1 into target cells is dependent upon binding of the viral envelope glycoprotein gp120 to CD4. In addition, several chemokine receptors function as HIV co-receptors and determine efficient infection of various cell types with HIV-1 strains. After binding, the HIV-1 envelope glycoproteins mediate fusion of viral and host cell membranes to complete the entry process. Once inside the cells, a process of viral replication occurs and through a budding process replicated viruses are released from infected cells, This eventually leads to cytolytic destruction of the infected cells. This sequence is repeated many times thereby significantly reducing the number of the target cells in the body, which is a severe and life-threatening material state often giving rise to eventual death of the infected individual.
Adenosine is a purine nucleoside present in plasma and other extracellular fluids. It is released into the extracellular space by various cell types and exerts an effect or other cells by binding to G-protein associated receptors on the cell membrane(1-2). The interaction of adenosine with its receptors initiates signal transduction pathways, progressing mainly the adenylate cyclase effector system, which utilizes cAMP as a second messenger. G-protein associated adenosine receptors are classified into four groups referred to as A1, A2a, A2b and A3. A1 and A3 receptors are coupled with Gi proteins and thus inhibit adenylate cyclase leading to a decrease in the level of intracellular cAMP. The A2a and A2b receptors are coupled to Gs proteins and thus activates adenylate cyclase, thereby increasing cAMP levels(3).
Among the physiological effects of extracellular adenosine are inhibition of cytokine release, inhibition of platelet aggregation, induction of erythropoietin production and modulation of lymphocyte function(4-6). Adenosine is also involved in the modulation of some central nervous system (CNS) functions, in wound healing, in diuresis and in controlling pain. Adenosine is capable of inducing proliferation in a wide range of normal cell types(7-10).